The danger signal extracellular ATP is involved in the immuno-mediated damage of alpha-sarcoglycan deficient muscular dystrophy.

The danger signal extracellular ATP is involved in the immuno-mediated damage of alpha-sarcoglycan deficient muscular dystrophy. Am J Pathol. 2018 Nov 15;: Authors: Gazzerro E, Baratto S, Assereto S, Baldassari S, Panicucci C, Raffaghello L, Scudieri P, De Battista D, Fiorillo C, Volpi S, Chaabane L, Malnati M, Messina G, Bruzzone S, Traggiai E, Grassi F, Minetti C, Bruno C Abstract In muscular dystrophies the muscle membrane fragility results in a tissue-specific increase of danger-associated molecules (DAMPs) and infiltration of inflammatory cells. The DAMP extracellular adenosine triphosphate (eATP) released by dying myofibers steadily activates muscle and immune purinergic receptors exerting dual negative effects: a direct damage linked to altered intracellular calcium homeostasis in muscle cells and an indirect toxicity through the "triggering" of the immune response and inhibition of regulatory T cells. Accordingly, pharmacological and genetic inhibition of eATP signaling improves the phenotype in models of chronic inflammatory diseases. In α-sarcoglycanopathy (LGMD2D), eATP effects may be further amplified since α-sarcoglycan extracellular domain binds eATP and displays an ecto-ATPase activity, thus controlling eATP concentration at the cell surface and attenuating the magnitude and/or the duration of eATP-induced signals. Here we show that in vivo blockade of the eATP/P2X purinergic pathway by a broad spectrum P2XR-antagoni...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research